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Probing for Answers

While most life scientists are focused on pushing back the frontiers of cell biology, physiology, and molecular biology, there exists a small and industrious subpopulation of researchers working intensively to create new tools to enable innovative research. A case in point is the BioCurrents Research Center ( BRC), which develops miniature electrochemical sensors for the detection of molecules crossing cell membranes.

The BRC is part of the Program in Molecular Physiology, a section of the Marine Biological Laboratory in Woods Hole, Massachusetts. The BRC is an essential part of the molecular physiology group, working with basic researchers and providing the tools necessary for answering novel questions about cellular transport and metabolism. In addition to working with local researchers, the BRC facility thrives on the collaborative environment of the Marine Biological Laboratory, which swarms with visiting scientists, students, and sunbathers in the summer months, and a few brave investigators willing to deal with the wind, ice, and snow during the winter months.

In 1996 the current director, Peter Smith, initiated the BRC as a facility for the design, construction, and use of miniature ion-selective probes. These probes detect gradients of particular ions in the vicinity of a cell. The center was funded by the NIH National Center for Research Resources, whose mission is to support technology driven research. During his tenure as director of the BRC, Smith has obtained patents on many of the probe technologies.

Smith enjoys leading the BioCurrents center from both a technical and a biological perspective. "The instrumentation offers insights into cell function that have never been seen before," he notes. "At first the challenge is to make the measurements, but the reward is [the production of] data that is completely new." The center currently functions as a probe modification facility, a source of novel probes (and other technologies), and as a location at which these tools can be applied to answering essential biological questions.

Although the probes are often distributed to other laboratories, their use is not always straightforward. "They need to be calibrated for each physiological environment," says Kasia Hammar, a technical specialist at the BRC. "It is essential to understand the probe technology before it can be used properly." During the development of a new probe, the staff at the BRC often collaborate with basic researchers to answer probe-related questions and, sometimes, to fine-tune the probe to reduce artifacts and variability induced by diverse media conditions. The probes need to be functional in the relatively benign cell-culture-media environment of a mammalian cell line, as well as in the extreme environments favored by, for example, an acidiphilic protist, normally found swimming about in streams and lakes of high acidity (pH 2 to 3). Creating a probe that can function in such a wide range of conditions, and adapting it to those environments, is a considerable technical challenge. Hammar finds this to be the most rewarding part of her job.

Because most of the funding is federal and not commercial, there is a large degree of creative freedom for the postdoctoral researchers involved in probe development. "I always wanted to be an inventor," mused Mark Messerli. "I could stay up all night thinking up new ideas." Messerli just recently moved up the ranks from postdoctoral researcher to staff scientist at the BRC. Although his background is in cell physiology and engineering, Messerli enjoys his current position, which fuses analytical chemistry, cell physiology, electronics, and optics. During his graduate work at Purdue University in West Lafayette, Indiana, he pursued basic questions about the ionic regulation of growing pollen tubes. He found that to answer some of the most intriguing questions, he had to build his own equipment, including a microscope-based video collection/photon counting system. He regrets that the tools that he developed during his Ph.D. were either not simple enough to rebuild in other labs or were too specific to apply to other research questions. His goal as a postdoctoral researcher is to create tools that are more widely useful, tools that can be easily produced and used to answer numerous biological questions.

Whereas many laboratories focus on a single system, research at the BRC addresses several systems through the creation and adaptation of novel tools. A constant influx of collaborators assures persistent and wide-ranging stimuli, with a great diversity of questions ranging from oxygen consumption of developing embryos to nitric oxide signaling in shark retinas.

Messerli's goal is to continue his work as a faculty member at an academic institution, where he will continue to develop the probe technologies that he has helped produce while collaborating with other scientists to answer basic cell biology questions.

Postdoctoral researchers at the BRC continue on to a wide variety of careers. Smith, the director, likes to talk about the many biologists-turned-engineers or -physicists who have come out of his group, as well as the engineers and physicists who, as a result of their BRC experiences, have begun to ask more life-science questions. Some postdoctoral researchers have gone on to industry, where there is enormous interest in the development of probes to detect pathological perturbations in homeostasis, such as increased blood glucose levels in diabetes or decreased oxygen consumption in embryos of low viability. Because of the growing interest in probe development from both biologists and engineers alike, the BRC may soon become part of a graduate program in conjunction with a local university. Currently graduate students at the BRC are hosted by other universities and advised by Smith, who has joint appointments at several other academic institutions. Additionally, some graduate students and postdoctoral researchers come to the center over the summer as part of the Grass Fellowship. "Progress at the BRC relies on the influx and imagination of new investigators in the form of students and postdoctoral researchers," says Smith.